This invention relates to the treatment of heart abnormalities and in particular to a method of increasing the force of contraction of the cardiac muscle (positive inotropic effect) and increasing the heart rate (positive chronotropic effect) without decreasing blook pressure (hypotensive effect) using NAPADE, a naturally occurring metabolite of procainamide and N-acetylprocainamide. The method is particularly suited for treating patients experiencing heart failure to increase the force of contraction of the heart muscle and in the treatment of cardiac arrhythmias.
Procainamide is a well known, widely prescribed compound used in the treatment of premature ventricular contractions and ventricular tachycardia, atrial fibrillation, and paroxysmal tachycardia. The primary use of procainamide is in the therapy of atrial fibrillation and other cardiac arrhythmias; see Goodman and Gilman, The Pharmacological Basic of Therapeutics, 5th Edition, 1975, Chapter 32, Antiarrhythmic Drugs.
Procainamide has the formula: ##STR1##
Desethyl-N-acetylprocainamide (NAPADE), also known as desethyl acecainide, has the structural formula: ##STR2## a molecular weight of 249, and is a naturally occurring metabolite of procainamide and N-acetylprocainamide (NAPA). NAPADE was first described by Dreyfuss et al: Metabolism of Procainamide in Rhesus Monkeys and Man, Clin. Pharmacol. Ther. 13:366-367 (1972) and later identified as a metabolite in humans treated with procainamide and NAPA by Taber et al: N-Desethylacecainide Is a Metabolite of Procainamide in Man, Drug Metab. Dispos. 7:346 (1979) and Ruo et al: Plasma Concentrations of Desethyl-N-acetylprocainamide in Patients Treated with Procainamide and N-acetylprocainamide, Ther. Drug. Monitor. 3:231-237 (1981). NAPADE was reported by Ruo to exhibit antifibrillatory activity in mice; Identification of Desethyl Procainamide in Patients: A New Metabolite of Procainamide, J. Pharmacol. Exp. Ther. 216:357-362 (1981).